Membrane-Active Singlet Oxygen Photogenerators as a Paradigm for Broad-Spectrum Antivirals: The Case of Halogenated (BOron)-DIPYrromethenes

• Authors: MARYEWSKI Xenia A.; KRASILNIKOV Maxim S.; STRAKOVÁ Petra; HOLOUBEK Jiří; FRČKOVÁ Tereza; PANINA Irina S.; KRYLOV Nikolay A.; GVOZDEV Daniil A.; DENISOV Vladislav S.; SEMENOV Alexey N.; LOTOSH Natalia Y.; SELISHCHEVA Alla A.; CHISTOV Alexey A.; GULYAK Evgeny L.; KOZHEMYAKIN Grigory L.; KORSHUN Vladimir A.; EFREMOV Roman G.; USTINOV Alexey V.; RŮŽEK Daniel; EYER Luděk; ALFEROVA Vera A.
• Year of publication: 2025
• Type: Article in Periodical
• Magazine / Source: ACS Applied Materials and Interfaces
• MU Faculty or unit: Faculty of Science
• web: https://doi.org/10.1021/acsami.4c17482
• Doi: http://dx.doi.org/10.1021/acsami.4c17482
• Keywords: BODIPY; enveloped viruses; membrane-targeting photosensitizer; singlet oxygen photogeneration; virus-inactivating activity
• Description: Enveloped viruses, such as flaviviruses and coronaviruses, are pathogens of significant medical concern that cause severe infections in humans. Some photosensitizers are known to possess virucidal activity against enveloped viruses, targeting their lipid bilayer. Here we report a series of halogenated difluoroboron-dipyrromethene (BODIPYs) photosensitizers with strong virus-inactivating activity. Our structure–activity relationship analysis revealed that BODIPY scaffolds with a heavy halogen atom demonstrate significant efficacy against both tick-borne encephalitis virus (TBEV; Flaviviridae family) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; Coronaviridae family) along with high singlet oxygen quantum yields. Moreover, select compounds also inactivated other enveloped viruses, such as herpes simplex virus type 1 and monkeypox virus. The nature and length of the alkyl side chain notably influenced the virus-inactivating activity of BODIPY molecules. Furthermore, molecular dynamics studies highlighted the critical importance of the positioning of the chromophore moiety within the lipid bilayer. As membrane-targeting photosensitizers, BODIPYs interact directly with virus particles, causing damage to the viral envelope membranes. Thus, TBEV pretreated with BODIPY was completely noninfective for lab mice. Consequently, BODIPY-based photosensitizers hold potential either as broad-spectrum virus-inactivating antivirals against a variety of phylogenetically unrelated enveloped viruses or as potent inactivators of viruses for the development of vaccines for preventing life-threatening emerging viral diseases.